4-Chloropyridine-2-carboxamide → 4-(4-Amino-2-fluorophenoxy)picolinamide

HRID 2377735Notes

Reaction equation

HRID 2377735 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([F:9])[CH:3]=1.CC(C)([O-])C.[K+].Cl[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([C:23]([NH2:25])=[O:24])[CH:18]=1>CN(C=O)C>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:17]2[CH:22]=[CH:21][N:20]=[C:19]([C:23]([NH2:25])=[O:24])[CH:18]=2)=[C:4]([F:9])[CH:3]=1

Participants

5

Reactant 3

HCID 3035434-Chloropyridine-2-carboxamideHCID 2735918Phenol, 4-amino-2-fluoro-HCID 23665647Potassium tert-butoxide

Product 1

HCID 231532054-(4-Amino-2-fluorophenoxy)picolinamideYield 82.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-amino-2-fluorophenol (0.81 g, 6.4 mmol, 1.0 eq) in DMF (6.5 mL) was treated with potassium tert-butoxide (0.79 g, 7.1 mmol, 1.1 eq) at room temperature and the reaction mixture was stirred for 1 h. 4-Chloropicolinamide (1.0 g, 6.4 mmol, 1.0 eq) was added and the reaction mixture was heated to 110 IC for 8 h. The reaction was cooled to room temperature and the reaction mixture quenched with water. The resulting heterogeneous solution was filtered and the solid material was washed with water. The solid was triturated with a small amount of MeOH followed by Et2O. The solid was filtered and dried in vacuo to afford the product (1.3 g, 82%) as a solid. 1H NMR (DMSO-d6) δ 8.49-8.50 (m, 1H), 8.12 (br s, 1H), 7.71 (br s, 1H), 7.35-7.36 (m, 1H), 7.14-7.16 (m, 1H), 7.01-7.06 (m, 1H), 6.44-6.47 (m, 2H), 5.53 (s, 2H); MS (ESI+) m/z 248 (M+H)+.

Workup

  1. temperaturethe reaction mixture was heated to 110 IC for 8 h
  2. customthe reaction mixture quenched with water
  3. filtrationThe resulting heterogeneous solution was filtered
  4. washthe solid material was washed with water
  5. customThe solid was triturated with a small amount of MeOH
  6. filtrationThe solid was filtered
  7. customdried in vacuo

Sources & evidence

ORD record
ord-6e3d8659ac884423bd61de6e60189166
Source dataset
uspto-grants-2008_12
Patent number
US07470693B2

Reaction notes

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